For several years we have been studying regulation of protein synthesis by membrane-bound versus free polyribosomes in liver. We have translated liver mRNA in both homologous (liver) and heterologous (reticulocyte) cell-free systems. Synthesis of albumin and ferritin has been used as markers for specific secretory versus intracellular proteins. Alterations in synthesis of these proteins and their respective mRNA levels in normal, regenerating, and toxically injured liver cells are currently in progress. Detailed evaluation of the synthetic and secretory mechanism for albumin, including characterization of prealbumin molecules, has been started. The major purpose of these studies is to determine whether levels of specific mRNA in a given ribosomal population or other factors regulate protein synthesis in the liver. Recently we have become interested in mechanisms for mRNA release, cytoplasmic transport, and polyribosomal attachment in eukaryotic cells. Our current feeling is that mRNA released from the nucleus exists in the form of messenger-ribonucleoprotein particles (mRNPs) and that specific protein factors in these particles may influence mRNA metabolism or function in eukaryotic cells. We have found that certain initiation factors form complexes with isolated mRNA and activity for at least one of the initiation factors, IF-MP, is present on reticulocyte mRNPs. We would like to continue these studies to determine the precise role of mRNPs in the eukaryotic initiation process and other parameters relevant to translation of mRNA. Information and technical advances from these studies will then be applied to liver cells of animals treated with a variety of agents or conditions known to alter liver metabolism or function; namely drug induced toxic liver injury, acute and chronic ETOH administration, protein or amino acid deprivation, partial hepatectomy and CC14 induced liver cirrhosis.